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Metformin for Preventing Frailty in High Risk Older Adults

二甲双胍预防高危老年人的衰弱

基本信息

批准号：
10165434
负责人：
Sara Elyse Espinoza
金额：
$ 30.75万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10165434
关键词：
Acceleration Adult Aging Anti-Inflammatory Agents Antidiabetic Drugs Applications Grants Cessation of life Chronic Clinical Closure by clamp Communities Data Defect Development Diabetes Mellitus Economics Elderly Enrollment Etiology Glucose Intolerance Goals Growth Health Health Care Costs Healthcare Hospitalization Hospitals Impairment Incidence Inflammation Institutionalization Insulin Insulin Resistance Intervention Link Long-Term Care Metformin Molecular Monitor Muscle NIH Program Announcements Older Population Outcome Pathogenesis Pathway interactions Patients Pharmaceutical Preparations Pharmacology Phosphorylation Physiological Placebos Plasma Play Population Population Group Prediabetes syndrome Prevalence Prevention Process Property Protein Kinase Randomized Research Risk Risk Factors Role Signal Transduction Societies Sterility Sulfonylurea Compounds Syndrome Testing Time Veterans adverse outcome age related aged aging population base cost disability effective intervention epidemiology study falls follow-up frailty glucose tolerance health care service high risk improved inflammatory marker insulin sensitivity insulin sensitizing drugs insulin signaling novel patient home care population based prevent response

项目摘要

ABSTRACT Frailty is a geriatric syndrome which leads to poor health outcomes in older adults, such as falls, disability, hospitalization, institutionalization, and death. Due to the dramatic growth in the U.S. aging population and the health care costs associated with frailty (estimated at more than $18 billion per year), frailty is a major health care problem. There has been little research into potential pharmacologic interventions that would delay or reduce the incidence of frailty. Thus, the major goal of this study is to test metformin as a novel intervention for the prevention of frailty. We propose that diabetes/insulin resistance and inflammation are major contributors to frailty, and that the use of metformin to modulate diabetes/insulin resistance and inflammation will prevent and/or ameliorate the progression of frailty. The rationale for testing metformin for frailty prevention is based on the following: 1) Insulin resistance has been linked to the pathogenesis of frailty and our own research shows that diabetes is a significant predictor of frailty onset or worsening in community-dwelling older adults; 2) Several studies have shown that frail older subjects (compared with non-frail) are under a state of chronic low grade “sterile” inflammation, as evidenced by increase plasma concentration of inflammatory markers; 3) In addition to frailty, inflammation also plays a key role in the pathogenesis of insulin resistance; 4) Metformin has both insulin sensitizing and anti-inflammatory properties, and; 5) Our analyzed clinical administrative data from 2,415 adult veterans with diabetes shows that those who were taking metformin as monotherapy were at 34% reduced risk of becoming frail compared to patients taking sulfonylureas. We hypothesize that metformin will lead to reduced inflammation and insulin resistance present in older glucose-intolerant subjects and that these changes will consequently prevent the onset and/or progression of frailty in this sub-population of older adults. We propose to study glucose intolerant subjects, a population which encompasses approximately one-third of older adults, and is most likely to benefit from metformin. To our knowledge, this research will be the first to study a potential intervention targeted toward a central mechanism involved in the etiology of frailty. We will also assess potential molecular mechanisms (insulin signaling, AMPK signaling, etc.) as potential cellular defects in frailty that are alleviated by metformin. Because of the enormous costs associated with frailty (both personal and economic), a treatment that prevents or delays frailty, even in a sub-population of older adults, would have a major positive impact in our society.

摘要